Publications by authors named "Min Zhao"

1,920 Publications

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TaSRO1 plays a dual role in suppressing TaSIP1 to fine tune mitochondrial retrograde signaling and enhance salinity stress tolerance.

New Phytol 2022 Jun 24. Epub 2022 Jun 24.

The Key Laboratory of Plant Development and Environment Adaptation Biology, Ministry of Education, School of Life Science, Shandong University, Qingdao, 266237, P. R. China.

Initially discovered in yeast, mitochondrial retrograde signaling has long been recognized as an essential in the perception of stress by eukaryotes. However, how to maintain the optimal amplitude and duration of its activation under natural stress conditions remains elusive in plants. Here, we show that TaSRO1, a major contributor to the agronomic performance of bread wheat plants exposed to salinity stress, interacted with a transmembrane domain-containing NAC transcription factor TaSIP1, which could translocate from the endoplasmic reticulum (ER) into the nucleus and activate a number of mitochondrial dysfunction stimulon (MDS) genes. Over-expression of TaSIP1 and TaSIP1-∆C (a form lacking the transmembrane domain) in wheat both compromised the plants' tolerance of salinity stress, highlighting the importance of precise regulation of this signal cascade during salinity stress. The interaction of TaSRO1/TaSIP1, in the cytoplasm, arrested more TaSIP1 on the membrane of ER, and in the nucleus, attenuated the trans-activation activity of TaSIP1, thus reducing the TaSIP1-mediated activation of MDS genes. Moreover, the over-expression of TaSRO1 rescued the inferior phenotype induced by TaSIP1 over-expression. Our study provides an orchestrating mechanism executed by the TaSRO1-TaSIP1 module that balances the growth and stress response via fine-tuning the level of mitochondria retrograde signaling.
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http://dx.doi.org/10.1111/nph.18340DOI Listing
June 2022

Generative Adversarial Network of Industrial Positron Images on Memory Module.

Entropy (Basel) 2022 Jun 7;24(6). Epub 2022 Jun 7.

College of Automation Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing 211106, China.

PET (Positron Emission Computed Tomography) imaging is a challenge due to the ill-posed nature and the low data of photo response lines. Generative adversarial networks have been widely used in computer vision and made great success recently. In our paper, we trained an adversarial model to improve the industrial positron images quality based on the attention mechanism. The innovation of the proposed method is that we build a memory module that focuses on the contribution of feature details to interested parts of images. We use an encoder to get the hidden vectors from a basic dataset as the prior knowledge and train the nets jointly. We evaluate the quality of the simulation positron images by MS-SSIM and PSNR. At the same time, the real industrial positron images also show a good visual effect.
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http://dx.doi.org/10.3390/e24060793DOI Listing
June 2022

Quinacrine is active in preclinical models of glioblastoma through suppressing angiogenesis, inducing oxidative stress and activating AMPK.

Toxicol In Vitro 2022 Jun 17:105420. Epub 2022 Jun 17.

Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China. Electronic address:

The poor prognosis of glioblastoma requires new innovative treatment strategies. We and others have shown that targeting tumor as well as angiogenesis in glioblastoma are effective therapeutic strategies. In line with these efforts, this work reveals that Quinacrine, an antimalarial drug, is a dual inhibitor of angiogenesis and glioblastoma. Using multiple glioblastoma cell lines, we found that Quinacrine inhibited proliferation and induced apoptosis in these cells, and acted in synergy with Temozolomide. Quinacrine potently inhibited tubular structure formations of glioblastoma microvascular endothelial cell (GMVEC) isolated from glioblastoma patients, especially for early stage tubular structure formation. Although Quinacrine induces apoptosis in GMVEC, the anti-angiogenic activity of Quinacrine is independent of its pro-apoptotic activity in GMVECs. Quinacrine inhibits glioblastoma angiogenesis and growth in vivo, and acts synergistically with Temozolomide in inhibiting glioblastoma growth in mice. Mechanistically, we found that Quinacrine acts on glioblastoma through inducing oxidative stress, impairing mitochondrial function and activating AMP-activated protein kinase (AMPK). Our work is the first to demonstrate the anti-angiogenic activity of Quinacrine. Our findings highlight Quinacrine as an attractive candidate to support treatment of glioblastoma.
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http://dx.doi.org/10.1016/j.tiv.2022.105420DOI Listing
June 2022

Efficacy and safety of befotertinib (D-0316) in patients with EGFR T790M mutated non-small cell lung cancer that had progressed after prior EGFR TKI therapy: A phase 2, multicenter, single-arm, open-label study.

J Thorac Oncol 2022 Jun 17. Epub 2022 Jun 17.

Department of Medical Oncology/Chemotherapy, The First Affiliated Hospital of University of Science and Technology of China, Anhui Provincial Hospital, Hefei, China.

Introduction: Befotertinib (D-0316) is a novel, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). This study evaluated befotertinib in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who developed an EGFR T790M mutation after progression on first- or second-generation EGFR TKI therapy.

Methods: This was a single-arm, open-label, phase 2 study at 49 hospitals across mainland China. Patients with locally advanced or metastatic NSCLC harboring EGFR T790M mutations with disease progression following prior first- or second- generation EGFR TKI therapy received oral befotertinib of 50 mg (cohort A) or 75-100 mg (cohort B) once daily. The primary endpoint was objective response rate (ORR) assessed by an independent review committee (IRC) in intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT03861156.

Results: A total of 176 patients and 290 patients were included in cohorts A (50 mg) and B (75-100 mg), respectively. At data-cutoff (August 15, 2021), IRC-assessed ORR was 67.6% (95% confidence interval [CI]: 61.9%-72.9%) in cohort B. The investigator-assessed ORR was 54.0% (95% CI: 46.3%-61.5%) in cohort A and 65.9% (95% CI: 60.1%-71.3%) in cohort B. Investigator-assessed disease control rate was 93.2% (95% CI: 88.4%-96.4%) in cohort A and 94.8% (95% CI: 91.6%-97.1%) in cohort B. Investigator-assessed intracranial ORR was 26.7% (95% CI: 7.8%-55.1%) in cohort A and 57.1% (95% CI: 34.0%-78.2%) in cohort B. The median investigator-assessed progression-free survival (PFS) was 11.0 (95% CI: 9.6-12.5) months in cohort A and 12.5 (95% CI: 11.1-13.8) months in cohort B. The median investigator-assessed intracranial PFS was 16.5 (95% CI: 8.6-not evaluable [NE]) months in cohort A and NE (95% CI: 13.8-NE) in cohort B. The overall survival was immature. Grade 3 or higher treatment-related adverse events and treatment-related serious adverse events occurred in 20.5% and 11.4% of patients in cohort A, and in 29.3% and 10.0% of patients in cohort B, respectively.

Conclusion: Befotertinib of 75-100 mg has satisfying efficacy and manageable toxicity in patients with locally advanced or metastatic NSCLC harboring T790M mutation with resistance to first- or second- generation EGFR TKIs. A phase 3 randomized trial is underway (NCT04206072).
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http://dx.doi.org/10.1016/j.jtho.2022.06.002DOI Listing
June 2022

Effects of the COVID-19 Lockdown on Air Pollutant Levels and Associated Reductions in Ischemic Stroke Incidence in Shandong Province, China.

Front Public Health 2022 27;10:876615. Epub 2022 May 27.

Department of Epidemiology, School of Public Health, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Background: Local governments in China took restrictive measures after the outbreak of COVID-19 to control its spread, which unintentionally resulted in reduced anthropogenic emission sources of air pollutants. In this study, we intended to examine the effects of the COVID-19 lockdown policy on the concentration levels of particulate matter with aerodynamic diameters of ≤1 μm (PM), ≤2.5 μm (PM), and ≤10 μm (PM), nitrogen dioxide (NO), sulfur dioxide (SO), ozone (O), and carbon monoxide (CO) and the potential subsequent reductions in the incidence of ischemic and hemorrhagic stroke in Shandong Province, China.

Methods: A difference-in-difference model combining the daily incidence data for ischemic and hemorrhagic stroke and air pollutant data in 126 counties was used to estimate the effect of the COVID-19 lockdown on the air pollutant levels and ischemic and hemorrhagic stroke incident counts. The avoided ischemic stroke cases related to the changes in air pollutant exposure levels were further estimated using concentration-response functions from previous studies.

Results: The PM, PM, PM, NO, and CO levels significantly decreased by -30.2, -20.9, -13.5, -46.3, and -13.1%, respectively. The O level increased by 11.5% during the lockdown compared with that in the counterfactual lockdown phase of the past 2 years. There was a significant reduction in population-weighted ischemic stroke cases (-15,315, 95% confidence interval []: -27,689, -2,942), representing a reduction of 27.6% (95% : -49.9%, -5.3%). The change in the number of hemorrhagic stroke cases was not statistically significant. The total avoided PM-, PM-, PM-, NO-, and CO-related ischemic stroke cases were 739 (95% : 641, 833), 509 (95% : 440, 575), 355 (95% : 304, 405), 1,132 (95% : 1,024, 1,240), and 289 (95% : 236, 340), respectively.

Conclusion: The COVID-19 lockdown indirectly reduced the concentration levels of PM, PM, PM, NO, and CO and subsequently reduced the associated ischemic stroke incidence. The health benefits due to the lockdown are temporary, and long-term measures should be implemented to increase air quality and related health benefits in the post-COVID-19 period.
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http://dx.doi.org/10.3389/fpubh.2022.876615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9197688PMC
June 2022

A Nomogram for Predicting Survival in Patients With Colorectal Cancer Incorporating Cardiovascular Comorbidities.

Front Cardiovasc Med 2022 27;9:875560. Epub 2022 May 27.

Chinese Academy of Medical Sciences and Peking Union Medical College, Fuwai Hospital, National Center for Cardiovascular Diseases, Beijing, China.

Background: Cardiovascular comorbidities (CVCs) affect the overall survival (OS) of patients with colorectal cancer (CRC). However, a prognostic evaluation system for these patients is currently lacking.

Objectives: This study aimed to develop and validate a nomogram, which takes CVCs into account, for predicting the survival of patients with CRC.

Methods: In total, 21,432 patients with CRC were recruited from four centers in China between January 2011 and December 2017. The nomogram was constructed, based on Cox regression, using a training cohort (19,102 patients), and validated using a validation cohort (2,330 patients). The discrimination and calibration of the model were assessed by the concordance index and calibration curve. The clinical utility of the model was measured by decision curve analysis (DCA). Based on the nomogram, we divided patients into three groups: low, middle, and high risk.

Results: Independent risk factors selected into our nomogram for OS included age, metastasis, malignant ascites, heart failure, and venous thromboembolism, whereas dyslipidemia was found to be a protective factor. The c-index of our nomogram was 0.714 (95% : 0.708-0.720) in the training cohort and 0.742 (95% : 0.725-0.759) in the validation cohort. The calibration curve and DCA showed the reliability of the model. The cutoff values of the three groups were 68.19 and 145.44, which were also significant in the validation cohort ( < 0.001).

Conclusion: Taking CVCs into account, an easy-to-use nomogram was provided to estimate OS for patients with CRC, improving the prognostic evaluation ability.
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http://dx.doi.org/10.3389/fcvm.2022.875560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9196079PMC
May 2022

A machine learning based model accurately predicts cellular response to electric fields in multiple cell types.

Sci Rep 2022 Jun 15;12(1):9912. Epub 2022 Jun 15.

Department of Applied Mathematics, University of California, Santa Cruz, CA, 95064, USA.

Many cell types migrate in response to naturally generated electric fields. Furthermore, it has been suggested that the external application of an electric field may be used to intervene in and optimize natural processes such as wound healing. Precise cell guidance suitable for such optimization may rely on predictive models of cell migration, which do not generalize. Here, we present a machine learning model that can forecast directedness of cell migration given a timeseries of previous directedness and electric field values. This model is trained using time series galvanotaxis data of mammalian cranial neural crest cells obtained through time-lapse microscopy of cells cultured at 37 °C in a galvanotaxis chamber at ambient pressure. Next, we show that our modeling approach can be used for a variety of cell types and experimental conditions with very limited training data using transfer learning methods. We adapt the model to predict cell behavior for keratocytes (room temperature, ~ 18-20 °C) and keratinocytes (37 °C) under similar experimental conditions with a small dataset (~ 2-5 cells). Finally, this model can be used to perform in silico studies by simulating cell migration lines under time-varying and unseen electric fields. We demonstrate this by simulating feedback control on cell migration using a proportional-integral-derivative (PID) controller. This data-driven approach provides predictive models of cell migration that may be suitable for designing electric field based cellular control mechanisms for applications in precision medicine such as wound healing.
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http://dx.doi.org/10.1038/s41598-022-13925-4DOI Listing
June 2022

Synthesis of multi-branched Au nanocomposites with distinct plasmon resonance in NIR-II window and controlled CRISPR-Cas9 delivery for synergistic gene-photothermal therapy.

Biomaterials 2022 Jun 7;287:121621. Epub 2022 Jun 7.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China. Electronic address:

Clinical implementation of photothermal therapy (PTT) is mainly hampered by limited tissue penetration, undesirable thermal damage to normal tissues, and thermotolerence induced by heat shock proteins (HSPs). To overcome these obstacles, we constructed a novel gene-photothermal synergistic therapeutic nanoplatform composed of a multi-branched Au nanooctopus (AuNO) core and mesoporous polydopamine (mPDA) shell, followed by CRISPR-Cas9 ribonucleoprotein (RNP) loading and then polyethylene glycol-folic acid (PEG-FA) coating. AuNO was simply synthesized by adjusting the ratio of cetyltrimethylammonium chloride (CTAC) and cetyltrimethylammonium bromide (CTAB), which showed significant localized surface plasmon resonances in the NIR-II window, and exhibited an excellent tissue penetration capability and high photothermal conversion efficiency (PCE, 47.68%). Even, the PCE could be further increased to 66.17% by mPDA coating. Furthermore, the sequential modification of [email protected] using RNP and PEG-FA can down-regulate HSP90α expression at tumor sites, enhance apoptosis and reduce the heat resistance of cancer cells. The synergistic effect of enhanced photothermal capacity and reduced thermoresistance addressed the multiple limitations of PTT, and presented excellent in vitro and in vivo antitumor efficacy, having great potential for the clinical application of PTT.
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http://dx.doi.org/10.1016/j.biomaterials.2022.121621DOI Listing
June 2022

High stability of autochthonous dissolved organic matter in karst aquatic ecosystems: Evidence from fluorescence.

Water Res 2022 Jul 7;220:118723. Epub 2022 Jun 7.

State Key Laboratory of Environmental Geochemistry, CAS, Institute of Geochemistry, Guiyang 550081, China.

Biological carbon pump (BCP) in karst areas has received intensive attention for years due to their significant contribution to the global missing carbon sink. The stability of autochthonous dissolved organic matter (Auto-DOM) produced by BCP in karst aquatic ecosystems may play a critical role in the missing carbon sink. However, the source of dissolved organic matter (DOM) in inland waters and its consumption by planktonic bacteria have not been thoroughly examined. Recalcitrant dissolved organic matter (RDOM) may exist in karst aquatic ecosystem as in the ocean. Through the study of the chromophoric dissolved organic matter (CDOM) and the interaction between CDOM and the planktonic bacterial community under different land uses at the Shawan Karst Water-carbon Cycle Test Site, SW China, we found that C2, as the fluorescence component of Auto-DOM mineralised by planktonic bacteria, may have some of the characteristics of RDOM and is an important DOM source in karst aquatic ecosystems. The stability ratio (Fmax) of Auto-DOM reached 89.6 ± 6.71% in winter and 64.1 ± 7.19% in spring. Moreover, correlation-based network analysis determined that the planktonic bacterial communities were controlled by different fluorescence types of CDOM, of which C1 (fresh Auto-DOM), C3 (conventional allochthonous DOM (Allo-DOM)) and C4 (the Allo-DOM mineralised by bacteria) were clustered in one module together with prevalent organic-degrading planktonic bacteria; C2 was clustered in another tightly combined module, suggesting specific microbial utilization strategies for the C2 component. In addition, some important planktonic bacterium and functional genes (including chemotrophic heterotrophs and photosynthetic bacteria) were found to be affected by high Ca and dissolved inorganic carbon (DIC) concentrations in karst aquatic ecosystems. Our research showed that Auto-DOM may be as an important carbon sink as the Allo-DOM in karst ecosystems, the former generally being neglected based on a posit that it is easily and first mineralized by planktonic bacteria.
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http://dx.doi.org/10.1016/j.watres.2022.118723DOI Listing
July 2022

Oncolytic virus expressing PD-1 inhibitors activates a collaborative intratumoral immune response to control tumor and synergizes with CTLA-4 or TIM-3 blockade.

J Immunother Cancer 2022 Jun;10(6)

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, Fujian, China

Background: Oncolytic viruses (OVs) are capable to inflame the tumor microenvironment (TME) and elicit infiltrating tumor-specific T cell responses. However, OV treatment negatively alters the cancer-immune set point in tumors to attenuate the antitumor immune response, which suggests the necessity of dissecting the immune landscape of the virus-treated tumors and developing novel strategies to maximize the potential of OVs. The aim of this study is to investigate the effect of the single-chain variable fragment (scFv)-armed OVs targeting PD-1 on the TME, and ultimately overcome localized immunosuppression to sensitize tumors to immunotherapies.

Methods: A tumor-selective oncolytic herpes simplex virus vector was engineered to encode a humanized scFv against human PD-1 (hPD-1scFv) (YST-OVH). The antitumor efficacy of YST-OVH was explored in multiple therapeutic mouse models. The neurotoxicity and safety of YST-OVH were evaluated in nonhuman primates. The precise dynamics in the TME involved in YST-OVH treatment were dissected using cytometry by time-of-flight (CyTOF).

Results: The identified hPD-1scFv showed superior T-cell activating activity. Localized delivery of hPD-1scFv by YST-OVH promotes systemic antitumor immunity in humanized PD-1 mouse models of established cancer. Immune profiling of tumors using CyTOF revealed the enhanced antitumor effect of YST-OVH, which largely relied on CD8 T cell activity by augmenting the tumor infiltration of effector CD8 T cells and establishment of memory CD8 T cells and reducing associated CD8 T cell exhaustion. Furthermore, YST-OVH treatment modified the cancer-immune set point of tumors coupled to coexpression of CTLA-4 and TIM-3 on exhausted CD8 T cells and high levels of CTLA-4 Treg cells. A combination approach incorporating anti-CTLA-4 or anti-TIM-3 further improved efficacy by increasing tumor immunogenicity and activating antitumor adaptive immune responses. Moreover, this therapeutic strategy showed no neurotoxicity and was well tolerated in nonhuman primates. The benefit of intratumoral hPD-1scFv expression was also observed in humanized mice bearing human cancer cells.

Conclusion: Localized delivery of PD-1 inhibitors by engineered YST-OVH was a highly effective and safe strategy for cancer immunotherapy. YST-OVH also synergized with CTLA-4 or TIM-3 blockade to enhance the immune response to cancer. These data provide a strong rationale for further clinical evaluation of this novel therapeutic approach.
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http://dx.doi.org/10.1136/jitc-2022-004762DOI Listing
June 2022

In vitro assessment of roles of PPP1R14B in cervical and endometrial cancer.

Tissue Cell 2022 May 31;77:101845. Epub 2022 May 31.

Department of Obstetrics and Gynecology, Shandong Provincial Third Hospital, Jinan 250031, China. Electronic address:

Cervical and endometrial cancers are common gynecologic cancers. Protein phosphatase 1 regulatory subunit 14B (PPP1R14B) is aberrantly expressed in several tumors, while its functions in cervical and endometrial cancers remain largely uncertain. The differentially expression of PPP1R14B in cervical and endometrial cancers was predicted by GEPIA2 and Human Protein Atlas databases. The diagnostic value was analyzed by AUC curve. The association between PPP1R14B expression and overall survival was predicted using Kaplan-Meier Plotter database. The function of PPP1R14B was investigated according to in vitro assessment. PPP1R14B and phosphorylation level of Akt were analyzed through western blotting. Cell proliferation was investigated by CCK-8 and EdU staining assays. Cell apoptosis was evaluated via TUNEL staining and caspase-3 activity assays. PPP1R14B level was upregulated in cervical and endometrial cancers, and it was associated with diagnosis and worse prognosis. PPP1R14B silencing constrained cell proliferation and promoted cell death in cervical and endometrial cancers cells. PPP1R14B knockdown suppressed activation of the Akt pathway. Re-activation of the Akt signaling reversed the anti-proliferative and cell death-promoting roles of PP1R14B knockdown in cervical and endometrial cancers cells. In conclusion, PPP1R14B knockdown represses cell proliferation and facilitates cell death by inhibiting the activation of the Akt signaling in cervical and endometrial cancers.
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http://dx.doi.org/10.1016/j.tice.2022.101845DOI Listing
May 2022

The selective serotonin reuptake inhibitor fluoxetine has direct effects at beta-cells to promote insulin secretion and increase beta-cell mass.

Diabetes Obes Metab 2022 Jun 8. Epub 2022 Jun 8.

Department of Diabetes, School of Cardiovascular and Metabolic Medicine & Sciences, Faculty of Life Sciences & Medicine, King's College London, UK.

Aims: Management of depression using fluoxetine has been associated with reductions in plasma glucose and glycated haemoglobin that are independent of changes in food intake and body weight. Fluoxetine reaches steady state concentrations of 0.3-2.6μmol/l in plasma following its long term use. This study aimed to investigate whether therapeutically relevant concentrations of fluoxetine regulate beta-cell function and improve glucose homeostasis.

Methods: Cell viability, insulin secretion, beta-cell proliferation and apoptosis were assessed following exposure of MIN6 beta-cells or isolated mouse and human islets to 0.1, 1 or 10μmol/l fluoxetine. The effect of fluoxetine (10mg/kg body weight) administration on glucose homeostasis and islet function was also examined in ob/ob mice.

Results: Exposure of MIN6 cells and mouse islets to 0.1 and 1μmol/l fluoxetine for 72 hours did not compromise cell viability but 10μmol/l fluoxetine significantly increased Trypan blue uptake. 1μmol/l fluoxetine significantly increased beta-cell proliferation and protected islet cells from cytokine-induced apoptosis. 1μmol/l fluoxetine also induced rapid and reversible potentiation of glucose-stimulated insulin secretion from islets isolated from mice, and from lean and obese human donors. Finally, intraperitoneal administration of fluoxetine to ob/ob mice over 14 days improved glucose tolerance and resulted in significant increases in beta-cell proliferation and enhanced insulin secretory capacity.

Conclusions: These data are consistent with a role for fluoxetine in regulating glucose homeostasis through direct effects at beta-cells. Fluoxetine thus demonstrates promise as a preferential antidepressant for patients with concomitant occurrence of depression and diabetes. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/dom.14791DOI Listing
June 2022

Ropivacaine with Dexmedetomidine or Dexamethasone in a Thoracic Paravertebral Nerve Block Combined with an Erector Spinae Plane Block for Thoracoscopic Lobectomy Analgesia: A Randomized Controlled Trial.

Drug Des Devel Ther 2022 26;16:1561-1571. Epub 2022 May 26.

Department of Anesthesiology, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical University, Tongji Shanxi Hospital, Taiyuan, 030032, People's Republic of China.

Objective: This study aimed to investigate the effect of ropivacaine with dexmedetomidine or dexamethasone in a thoracic paravertebral nerve block (TPVB) combined with an erector spinae plane block (ESPB) for thoracoscopic lobectomy analgesia.

Methods: A total of 97 patients undergoing thoracoscopic lobectomy under general anesthesia were enrolled in this study and randomly divided into three groups, ie, a ropivacaine group (Group R), a ropivacaine + dexmedetomidine group (Group R1), and a ropivacaine + dexamethasone group (Group R2). Ultrasound-guided TPVB combined with an erector spinae plane block was given after anesthesia induction. The following were applied to each group: Group R received 30 mL of 0.5% ropivacaine + 5 mL of a normal saline mixture; Group R1 received 30 mL of 0.5% ropivacaine + 5 mL of a 1 μg/kg dexmedetomidine mixture; Group R2 received 30 mL of 0.5% ropivacaine + 5 mL of an 8 mg dexamethasone mixture. The primary observation index was the time to the first postoperative remedial analgesia. The secondary observation indexes were the intraoperative consumption of propofol and sufentanil, time to waking from anesthesia, time to extubation, postoperative numerical rating scaltpe (NRS) score, postoperative sufentanil consumption, remedial analgesic dosage, and adverse reactions.

Results: When compared with Group R, the time to first postoperative remedial analgesia was longer, the intraoperative and postoperative sufentanil consumption and flurbiprofen axetil remedial analgesic dose were lower, and the time to waking from anesthesia and time to extubation were shorter in groups R1 and R2 (P < 0.05). The NRS scores at 1, 6, 12, and 24 h postoperatively in groups R1 and R2 were lower than in Group R at the same time points (P < 0.05).

Conclusion: Ropivacaine with dexmedetomidine or dexamethasone in TPVB combined with ESPB could prolong the time to first postoperative remedial analgesia, reduce perioperative sufentanil and postoperative remedial analgesic drug consumption, and decrease the postoperative NRS score in patients undergoing thoracoscopic lobectomy.
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http://dx.doi.org/10.2147/DDDT.S366428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9152436PMC
June 2022

Serum Neutralizing Antibody Titers 12 months after COVID-19 mRNA Vaccination: Correlation to Clinical Variables in an Adult, US-Population.

Clin Infect Dis 2022 May 26. Epub 2022 May 26.

Department of Medicine, Yale School of Medicine, New Haven, CT, USA.

Background: We studied whether comorbid conditions impact strength and duration of immune responses after SARS-CoV-2 mRNA vaccination in a US-based, adult population.

Methods: Sera (pre-and-post-BNT162b2 vaccination) were tested serially up to 12 months after two doses of vaccine for SARS-CoV-2-anti-Spike neutralizing capacity by pseudotyping assay in 124 individuals; neutralizing titers were correlated to clinical variables with multivariate regression. Post-booster (third dose) effect was measured at 1 and 3 months in 72 and 88 subjects respectively.

Results: After completion of primary vaccine series, neutralizing antibody IC50 values were high at one month (14-fold increase from pre-vaccination), declined at six months (3.3-fold increase), and increased at one month post-booster (41.5-fold increase). Three months post-booster, IC50 decreased in COVID-naïve individuals (18-fold increase) and increased in prior COVID-19 + individuals (132-fold increase). Age >65 years (β=-0.94, p = 0.001) and malignancy (β=-0.88, p = 0.002) reduced strength of response at 1 month. Both neutralization strength and durability at 6 months, respectively, were negatively impacted by end-stage renal disease [(β=-1.10, p = 0.004); (β=-0.66, p = 0.014)], diabetes mellitus [(β=-0.57, p = 0.032); (β=-0.44, p = 0.028)], and systemic steroid use [(β=-0.066, p = 0.032); (β=-0.55, p = 0.037)]. Post-booster IC50 was robust against WA-1 and B.1.617.2. Post-booster neutralization increased with prior COVID-19 (β = 2.9, p-value < 0.0001), and malignancy reduced neutralization response (β=-0.68, p = 0.03), regardless of infection status.

Conclusion: Multiple clinical factors impact the strength and duration of neutralization response post-primary series vaccination, but not the post-booster dose strength. Malignancy was associated with lower booster-dose response regardless of prior COVID infection, suggesting a need for clinically guided vaccine regimens.
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http://dx.doi.org/10.1093/cid/ciac416DOI Listing
May 2022

M2-Macrophage-Derived Exosomes Promote Meningioma Progression through TGF- Signaling Pathway.

J Immunol Res 2022 20;2022:8326591. Epub 2022 May 20.

Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu 610041, China.

Tumor-associated macrophages (TAMs) have been shown to be an essential component of the tumor microenvironment and facilitate the proliferation and invasion of a variety of malignancies. However, the contribution of TAMs to meningioma progression has not been characterized in detail. In this study, we aimed to discover a novel regulatory pathway by which exosome-mediated M2-polarized macrophages participate in meningioma tumorigenesis and progression. . First, the distribution and functional phenotype of macrophages in meningioma tissues were assessed by immunohistochemistry. Macrophage-derived exosomes (MDEs) were characterized, and further cell coculture experiments were performed to explore the effects of M2-MDEs on the proliferation, migration, and invasion of meningioma cells. RNA sequencing was used to analyze the transcriptomic signatures in meningioma cells treated with M2-MDEs. Three-dimensional tumorspheres and xenograft tumor models were used to evaluate the effects of M2-MDEs on meningioma tumorigenesis and development. . We found that M2 macrophages were enriched in meningioma tissue. Coculture with meningioma cells induced the M2 polarization of macrophages. We also found that M2-MDEs were able to significantly promote cell proliferation, cell migration, cell invasion, and tumorigenesis in meningiomas. Bioinformatic analysis suggested that the TGF- pathway was activated in meningioma cells treated with M2-MDEs. Functional experiments demonstrated that blocking the TGF- signaling pathway could effectively reverse the tumor-promotive effects mediated by M2-MDEs. . Overall, our study showed that M2-MDEs promoted meningioma development and invasion by activating the TGF- signaling pathway. Targeting exosome-mediated intercellular communication in the tumor microenvironment may be a novel therapeutic strategy for meningioma patients.
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http://dx.doi.org/10.1155/2022/8326591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9146444PMC
June 2022

Regulating Root Fungal Community Using for Resistance in .

Front Microbiol 2022 12;13:850917. Epub 2022 May 12.

College of Life Sciences, Northeast Forestry University, Harbin, China.

Plant-associated microbes play important roles in plant health and disease. is often found in the plant rhizosphere, and its possible functions are not well known, especially in medical plants. isolated from ginseng soil was used to investigate its effects on plant disease. The promoting properties and interactions with rhizospheric microorganisms were investigated in a medium. Further, a pot experiment was conducted to explore its effects on ginseng root rot disease. Physicochemical properties, high-throughput sequencing, network co-occurrence, distance-based redundancy analysis (db-RDA), and correlation analysis were used to evaluate their effects on the root rot pathogen. The results showed that YW25 had a high indoleacetic acid production capacity, and the maximum yield was 141.37 mg/L at 4 days. The growth of YW25 was inhibited by some probiotics (, , , , etc.) and potential pathogens (, , etc.), but it did not show sensitivity to the soil-borne pathogen . Pot experiments showed that could significantly alleviate the diseases caused by , and increased the available nitrogen and phosphorus content in rhizosphere soil. In addition, it enhanced the activities of soil sucrase and acid phosphatase. High-throughput results showed that the inoculation of with changed the microbial community structure of ginseng, stimulated the plant to recruit more plant growth-promoting bacteria, and constructed a more stable microbial network of ginseng root. In this study, we found and proved the potential of as a biocontrol agent against , providing a new idea for controlling soil-borne diseases of ginseng by regulating rhizosphere microorganisms.
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http://dx.doi.org/10.3389/fmicb.2022.850917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9133625PMC
May 2022

From COVID-19 to Sarcoidosis: How Similar Are These Two Diseases?

Front Immunol 2022 9;13:877303. Epub 2022 May 9.

Department of Respiratory and Critical Care Medicine, The Second Hospital of Jilin University, Changchun, China.

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), leads to the dysregulation of the immune system, exacerbates inflammatory responses, and even causes multiple organ dysfunction syndrome in patients with severe disease. Sarcoidosis is an idiopathic granulomatous multisystem disease characterized by dense epithelioid non-necrotizing lesions with varying degrees of lymphocytic inflammation. These two diseases have similar clinical manifestations and may also influence each other and affect their clinical courses. In this study, we analyzed some possible connections between sarcoidosis and COVID-19, including the role of the renin-angiotensin system in the respiratory system, immune response, and cell death pathways, to understand the underlying mechanisms of SARS-CoV-2 infection, predisposing patients to severe forms of COVID-19. This review will provide a new prospect for the treatment of COVID-19 and an opportunity to explore the pathogenesis and development of sarcoidosis.
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http://dx.doi.org/10.3389/fimmu.2022.877303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9124764PMC
May 2022

Triple-serotype chimeric oncolytic adenovirus exerts multiple synergistic mechanisms against solid tumors.

J Immunother Cancer 2022 May;10(5)

Department of General Surgery, Huashan Hospital, Cancer Metastasis Institute, Fudan University, Shanghai 200040, China

Background: Oncolytic virotherapy has become an important branch of cancer immunotherapy. This study investigated the efficacy of an oncolytic adenovirus (OAV), OncoViron, with synergistic mechanisms in the treatment of multiple solid tumors.

Methods: An OAV, OncoViron, was constructed and investigated by cytological experiments and implanted tumor models of multiple solid tumor cell lines to certify its anticancer efficacy, the synergistic effects of viral oncolysis and transgene anticancer activity of OncoViron, as well as oncolytic virotherapy combined with immunotherapy, were also verified.

Results: The selective replication of OncoViron mediated high expression of anticancer factors, specifically targeted a variety of solid tumors and significantly inhibited cancer cell proliferation. On a variety of implanted solid tumor models in immunodeficient mice, immunocompetent mice, and humanized mice, OncoViron showed great anticancer effects on its own and in combination with programmed death 1 (PD-1) antibody and chimeric antigen receptor (CAR) T cells. Pathological examination, single-cell sequencing, and spatial transcriptome analysis of animal implanted tumor specimens confirmed that OncoViron significantly altered the gene expression profile of infected cancer cells, not only recruiting a large number of lymphocytes, natural killer cells, and mononuclear macrophages into tumor microenvironment (TME) and activated immune cells, especially T cells but also inducing M1 polarization of macrophages and promoting the release of more immune cytokines, thereby remodeling the TME for coordinating PD-1 antibody or CAR T therapy.

Conclusions: The chimeric OncoViron is a novel broad-spectrum anticancer product with multiple mechanisms of synergistic and potentiated immunotherapy, creating a good opportunity for combined immunotherapy against solid tumors.
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http://dx.doi.org/10.1136/jitc-2022-004691DOI Listing
May 2022

Efficacy of probiotics against dental caries in children: a systematic review and meta-analysis.

Crit Rev Food Sci Nutr 2022 May 24:1-18. Epub 2022 May 24.

Department of Gastroenterology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.

Dental caries causes serious consequences and the financial burden of society especially in children with high morbidity rate. Here we carried out a meta-analysis to systematically evaluate the efficacy of probiotics against dental caries in children. Forty-three RCTs were eligible for this meta-analysis after searching the PubMed, Cochrane and Web of Science from the inception through October 2021. Pooled estimates demonstrated that treatment with probiotics significantly reduced noncavitated (dicdas2-6mft) (SMD = -0.18, 95% CI: -0.3 to -0.06,  = 0.002) and cavitated (dicdas5-6mft) carious lesions in children (SMD = -0.32, 95% CI: -0.5 to 0.14,  = 0.0004). Probiotics also reduced prevalence of noncavitated (dicdas2-6mft) carious lesions (RR = 0.8, 95% CI: 0.67 to-0.97,  = 0.02). Salivary was declined after intervention (SMD = -1.17, 95% CI: -1.85 to -0.5,  = 0.0007), while counts were upregulated (SMD = 1.19, 95% CI: 0.46-1.92,  = 0.001). However, no significant effects in total bacteria counts and salivary pH were observed. Our findings suggest that probiotics especially could be a promising therapeutic strategy for clinical applications in children dental caries.
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http://dx.doi.org/10.1080/10408398.2022.2077693DOI Listing
May 2022

Age and sex specific reference intervals of 13 hematological analytes in Chinese children and adolescents aged from 28 days up to 20 years: the PRINCE study.

Clin Chem Lab Med 2022 Jul 24;60(8):1250-1260. Epub 2022 May 24.

Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, P.R. China.

Objectives: Pediatric Reference Intervals in China (PRINCE) is a nationwide initiative that aims to establish and validate harmonized reference intervals (RIs) for Chinese children and adolescents, in which 15,150 healthy volunteers aged up to 20 years were recruited from 11 centers to establish RIs and 7,557 children and adolescents were enrolled from 21 centers to validate RIs.

Methods: The complete blood cell counts (CBC) of venous whole blood were measured by hematology analyzers through Sysmex systems in different centers. Age- and sex-specific RIs were calculated according to the guidelines.

Results: Unlike adults with certain levels of analyte concentrations, hematological parameters of children changed through growth and development. Red blood cell counts, hemoglobin, and hematocrit increased with age, and revealed higher concentrations in boys than girls after puberty. White blood cell counts and platelet counts showed significant higher levels than adults before 2 years of age, and then gradually decreased without distinct sex differences. In addition, lymphocyte counts decreased with age while neutrophil counts showed an opposite trend. The lower and upper limits of pediatric RIs of CBC were different from those of adults.

Conclusions: The validation of RIs indicated that the PRINCE study provided a version of RIs suitable for most of regions in China. This first harmonized pediatric RIs of CBC across China provided a robust database to understand the dynamic changes of hematologic parameters from birth to adolescence, and will contribute to clinical diagnosis and prognosis evaluation for pediatric patients as well.
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http://dx.doi.org/10.1515/cclm-2022-0304DOI Listing
July 2022

Association between short-term exposure to ambient PM and PM and forced vital capacity in Chinese children and adolescents.

Environ Sci Pollut Res Int 2022 May 23. Epub 2022 May 23.

Department of Epidemiology, School of Public Health, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.

This study aims to examine the association between short-term exposure to ambient PM, PM, and PM and forced vital capacity (FVC). Population data were obtained from a school-based cross-sectional survey in Shandong in 2014. Distributed lag non-linear models were used to examine the association between exposure to PM, PM, and PM and FVC at the day of FVC measurement and the previous 6 days (lag 0 to 6 days). A total of 35,334 students aged 9 to 18 years were included in the study, and the mean exposure concentrations of ambient PM, PM, and PM for them were 47.4 (standard deviation [SD] = 21.3) μg/m, 32.8 (SD = 32.2) μg/m, and 80.1 (SD = 47.7) μg/m, respectively. An inter-quartile range (IQR, 24 μg/m) increment in exposure to PM was significantly associated with a lower FVC at lag 0 and lag 1 day (β =  - 80 mL, 95% CI =  - 119, - 42, and β =  - 37 mL, 95% CI =  - 59, - 16, respectively), and an IQR (54 μg/m) increment in exposure to PM was significantly associated with a lower FVC at lag 0 and lag 1 day (β =  - 57 mL, 95% CI =  - 89, - 18, and β =  - 34 mL, 95% CI =  - 56, - 12, respectively) after adjustment for gender, age, body mass index category, residence, month of the survey, intake of eggs, intake of milk, physical activity, and screen time. No significant associations were observed for PM. The inverse associations of PM and PM with FVC were larger in males, younger children, those overweight or obese, and those with insufficient physical activity levels. Short-term exposure to ambient PM and PM was associated with decreased FVC, and PM may be the primary fraction of PM causing the adverse pulmonary effects. Our findings emphasize the need to address ambient PM, especially PM, pollution for affecting pulmonary health in children and adolescents.
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http://dx.doi.org/10.1007/s11356-022-20842-6DOI Listing
May 2022

The ethanolic extract of Artemisia anomala exerts anti-inflammatory effects via inhibition of NLRP3 inflammasome.

Phytomedicine 2022 Jul 10;102:154163. Epub 2022 May 10.

Laboratory of Natural Product Drugs, State Key Laboratory of Biotherapy and Cancer Center, West China Medical School, West China Hospital, Sichuan University, Chengdu 610041, PR China.

Background: Artemisia anomala S. Moore (Compositae), known as "Nan-Liu-Ji-Nu" in traditional Chinese medicine (TCM), has been used to treat many inflammatory diseases, including enteritis, acute icteric hepatitis, rheumatism, toothache, tonsillitis, and chronic bronchitis, for centuries. Our preliminary studies have demonstrated that the ethanolic extract of A. anomala (EAA) might be with the potential of inhibiting the activation of the NLRP3 inflammasome. However, the anti-inflammatory activity of EAA based on NLRP3 inflammasome inhibition is still unclear.

Purpose: This work aimed to elucidate the anti-inflammatory mechanism of EAA by inhibiting NLRP3 inflammasome activation.

Methods: Lipopolysaccharide (LPS)-primed bone marrow-derived macrophages (BMDMs) were used to evaluate the inhibitory effects on NLRP3 inflammasome activation. The level of IL-1β was determined by ELISA. The expression levels of IL-1β, caspase-1, NLRP3, and ASC were assayed using western blot analysis. ASC oligomerization and speck formation were detected by immunofluorescence microscopy. The measurements of intracellular chloride and potassium were conducted using N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide (MQAE) probe assay and inductively coupled plasma-optical emission spectrometry (ICP-OES), respectively. Mitochondrial reactive oxygen species (mtROS) were examined using the MitoSOX method. Acridine orange (AO) staining was used to detect the permeability of the lysosomal membrane. A DSS-induced ulcerative colitis model was established to evaluate the anti-inflammatory effects of EAA in vivo. Finally, high-performance liquid chromatography (HPLC) was employed to identify and quantify the major constituents of EAA.

Results: In BMDMs, EAA significantly inhibited the release of IL-1β induced by LPS. The mechanistic study revealed that EAA inhibited NLRP3 inflammasome activation by blocking the oligomerization of ASC and suppressed the LPS-induced priming step. Furthermore, EAA protected lysosomes by inhibiting the TAK1-JNK pathway, thereby inhibiting the assembly of downstream NLRP3 inflammasome and the production of IL-1β. In addition, EAA exerted potent protective effects in an ulcerative colitis model by decreasing the content of colonic IL-1β and alleviating the process of ulcerative colitis. HPLC analysis identified eight main components of EAA, including isofraxidin (1), quercetin-7-O-β-D-glucopyranoside (2), apigenin-7-O-β-D-glucopyranoside (3), 7-methoxycoumarin (4), quercetin (5), luteolin (6), kaempferol (7), and eupatorin (8), Of these compounds, quercetin and kaempferol were found to be the most potent ingredients.

Conclusion: These findings collectively reveal that EAA exerts anti-inflammatory effects by both suppressing the NLRP3 priming step and protecting lysosomes to inhibit NLRP3 inflammasome activation, suggesting that this traditional herbal medicine might be used to treat NLRP3-driven inflammatory diseases.
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http://dx.doi.org/10.1016/j.phymed.2022.154163DOI Listing
July 2022

Analysis of rhodopsin G protein-coupled receptor orthologs reveals semiochemical peptides for parasite (Schistosoma mansoni) and host (Biomphalaria glabrata) interplay.

Sci Rep 2022 May 17;12(1):8243. Epub 2022 May 17.

Centre for Bioinnovation, University of the Sunshine Coast, Maroochydore, QLD, 4558, Australia.

Schistosomiasis is a medically significant disease caused by helminth parasites of the genus Schistosoma. The schistosome life cycle requires chemically mediated interactions with an intermediate (aquatic snail) and definitive (human) host. Blocking parasite development within the snail stage requires improved understanding of the interactions between the snail host and the Schistosoma water-borne free-living form (miracidium). Innovations in snail genomics and aquatic chemical communication provide an ideal opportunity to explore snail-parasite coevolution at the molecular level. Rhodopsin G protein-coupled receptors (GPCRs) are of particular interest in studying how trematode parasites navigate towards their snail hosts. The potential role of GPCRs in parasites makes them candidate targets for new antihelminthics that disrupt the intermediate host life-cycle stages, thus preventing subsequent human infections. A genomic-bioinformatic approach was used to identify GPCR orthologs between the snail Biomphalaria glabrata and miracidia of its obligate parasite Schistosoma mansoni. We show that 8 S. mansoni rhodopsin GPCRs expressed within the miracidial stage share overall amino acid similarity with 8 different B. glabrata rhodopsin GPCRs, particularly within transmembrane domains, suggesting conserved structural features. These GPCRs include an orphan peptide receptor as well as several with strong sequence homologies with rhabdomeric opsin receptors, a serotonin receptor, a sulfakinin (SK) receptor, an allatostatin-A (buccalin) receptor and an FMRFamide receptor. Buccalin and FMRFa peptides were identified in water conditioned by B. glabrata, and we show synthetic buccalin and FMRFa can stimulate significant rates of change of direction and turn-back responses in S. mansoni miracidia. Ortholog GPCRs were identified in S. mansoni miracidia and B. glabrata. These GPCRs may detect similar ligands, including snail-derived odorants that could facilitate miracidial host finding. These results lay the foundation for future research elucidating the mechanisms by which GPCRs mediate host finding which can lead to the potential development of novel anti-schistosome interventions.
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http://dx.doi.org/10.1038/s41598-022-11996-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9114394PMC
May 2022

Label-free fluorescence detection of hydrogen peroxide and glucose based on the Ni-MOF nanozyme-induced self-ligand emission.

Mikrochim Acta 2022 05 16;189(6):219. Epub 2022 May 16.

School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, 150001, China.

A bifunctional Ni-MOF nanosheet was synthesized and developed for label-free fluorescent detection of HO and glucose. The Ni-MOF exhibited intrinsic peroxidase-like activity and its catalytic activity was demonstrated to be originated from the hydroxyl radicals (•OH) produced in catalytic process. Since the generated •OH enabled terephthalic acid, the non-fluorescent organic ligand of Ni-MOF, to form a strongly fluorescent 2-hydroxy terephthalic acid, the Ni-MOF nanozyme was endowed with dual-function properties of mimicking peroxidase and emitting fluorescence. Based on this bifunctional Ni-MOF nanozyme, the proposed label-free fluorescence sensing strategy was applied to detecting HO and glucose with wide linear ranges of 0.1-20 mM and 8-30 μM, and low detection limits of 4.0 × 10 M and 4.0 × 10 M, respectively. Furthermore, the bifunctional Ni-MOF-based label-free sensing platform was successfully used for the glucose detection in human serum samples, showing good reproducibility and high accuracy. This strategy provides a green and sensitive method for the determination of small biomolecules in practical applications by the combination of enzyme cascade reaction.
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http://dx.doi.org/10.1007/s00604-022-05313-6DOI Listing
May 2022

Crystallographic landscape of SHP2 provides molecular insights for SHP2 targeted drug discovery.

Med Res Rev 2022 May 16. Epub 2022 May 16.

School of Pharmaceutical Sciences, Zhengzhou University, 450001, Henan, Zhengzhou, China.

The protein tyrosine phosphatase SHP2 encoded by PTPN11 is a promising therapeutic target for cancer therapy. The dynamic change of SHP2 between closed and open conformations under either physiological or pathological conditions provides opportunities to design SHP2 inhibitors for treating SHP2-related diseases. To date, several SHP2 allosteric inhibitors have advanced into clinical trials as mono- or combined therapy of cancers. In this review, we provide an overview on the structural landscape of SHP2 under physiological and pathological conditions and also comprehensively analyze the binding models of SHP2/inhibitor complexes. Structural features of SHP2 under pathological conditions and co-crystal structures of SHP2/inhibitor complexes will definitely facilitate structure-guided design of SHP2 inhibitors. Finally, proteolysis targeting chimeric (PROTAC) based SHP2 degraders have shown therapeutic promise for cancer therapy and are also briefly discussed. We hope this review could provide crystallographic landscape for SHP2 targeted drug discovery.
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http://dx.doi.org/10.1002/med.21890DOI Listing
May 2022

Actin Dynamics as a Multiscale Integrator of Cellular Guidance Cues.

Front Cell Dev Biol 2022 27;10:873567. Epub 2022 Apr 27.

Institute for Physical Science and Technology, University of Maryland, College Park, MD, United States.

Migrating cells must integrate multiple, competing external guidance cues. However, it is not well understood how cells prioritize among these cues. We investigate external cue integration by monitoring the response of wave-like, actin-polymerization dynamics, the driver of cell motility, to combinations of nanotopographies and electric fields in neutrophil-like cells. The electric fields provide a global guidance cue, and approximate conditions at wound sites . The nanotopographies have dimensions similar to those of collagen fibers, and act as a local esotactic guidance cue. We find that cells prioritize guidance cues, with electric fields dominating long-term motility by introducing a unidirectional bias in the locations at which actin waves nucleate. That bias competes successfully with the wave guidance provided by the bidirectional nanotopographies.
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http://dx.doi.org/10.3389/fcell.2022.873567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9092214PMC
April 2022

Anti-saccade as a Tool to Evaluate Neurocognitive Impairment in Alcohol Use Disorder.

Front Psychiatry 2022 27;13:823848. Epub 2022 Apr 27.

Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

It has been widely shown that chronic alcohol use leads to cognitive dysfunctions, especially inhibitory control. In an extension of the traditional approach, this research field has benefited from the emergence of innovative measures, among which is an anti-saccade, allowing direct and sensitive measure of the eye movements indexing attention bias to alcohol-related cues and the capability of inhibiting the reflexive saccades to the cues. During the past decade, there are numerous reports showing that drinkers make more unwanted reflexive saccades and longer latency in the anti-saccade task. These increased errors are usually explained by the deficits in inhibitory control. It has been demonstrated that inhibitory control on eye movement may be one of the earliest biomarkers of the onset of alcohol-related cognitive impairments. This review summarizes how an anti-saccade task can be used as a tool to investigate and assess the cognitive dysfunctions and the early detection of relapsing risk of alcohol dependence.
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http://dx.doi.org/10.3389/fpsyt.2022.823848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9094713PMC
April 2022

Impact of adverse childhood experiences on the symptom severity of different mental disorders: a cross-diagnostic study.

Gen Psychiatr 2022 22;35(2):e100741. Epub 2022 Apr 22.

Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Adverse childhood experiences have a significant impact on different mental disorders.

Objective: To compare differences in adverse childhood experiences among those with different mental disorders and their relationships in a cross-disorder manner.

Methods: The study included 1513 individuals aged ≥18 years : 339 patients with substance use disorders, 125 patients with schizophrenia, 342 patients with depression, 136 patients with bipolar disorder, 431 patients with obsessive-compulsive disorder (OCD), and 140 healthy controls. The Early Trauma Inventory Self Report-Short Form was used to investigate childhood traumatic experiences, and the Addiction Severity Index, Positive and Negative Syndrome Scale, Hamilton Depression Scale, Young Mania Rating Scale, and Yale-Brown Obsessive-Compulsive Scale were used to assess mental disorder severity. Correlation and multivariate logistic regression were analysed between adverse childhood experiences and clinical features.

Results: Levels of adverse childhood experiences were significantly different among different mental disorders. Moreover, 25.8% of patients with substance use disorders reported childhood trauma, which was significantly higher than found in the other four psychiatric disorder groups. Emotional abuse scores were positively correlated with disease severity: the higher the total trauma score, the more severe the mental disorder.

Conclusions: Adverse childhood experiences are a common phenomenon in those with mental disorders, and the level of trauma affects mental disorder severity. Emotional abuse is closely related to many mental disorders. The incidence or severity of mental disorders can be reduced in the future by reducing the incidence of adverse childhood experiences or by timely intervention in childhood trauma.
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http://dx.doi.org/10.1136/gpsych-2021-100741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9036421PMC
April 2022

Increasing N,N-dimethylacetamide degradation and mineralization efficiency by co-culture of Rhodococcus ruber HJM-8 and Paracoccus communis YBH-X.

Chemosphere 2022 Sep 10;303(Pt 1):134935. Epub 2022 May 10.

College of Biological and Environmental Engineering, Zhejiang Shuren University, Hangzhou 310015, China; Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province, Interdisciplinary Research Academy, Zhejiang Shuren University, Hangzhou 310015, China. Electronic address:

In this work, Rhodococcus ruber HJM-8 and Paracoccus communis YBH-X were isolated and used to enhance N,N-dimethylacetamide (DMAC) degradation and mineralization efficiencies. The monoculture and co-culture of the two strains for DMAC degradation were compared; results indicated that, a degradation efficiency of 97.62% was obtained in co-culture, which was much higher than that of monocultures of HJM-8 (57.34%) and YBH-X (34.02%). The degradation mechanism showed that co-culture could efficiently improve extracellular polymeric substances production, electron transfer, and microbial activity. Meanwhile, the mineralization mechanism suggested that acetate was the dominant intermediate which had an inhibitory effect on HJM-8, and co-culture was conducive to mineralization due to the high performance of acetate conversion and Na K-ATPase vitality. Besides, a pathway of DMAC biodegradation was proposed for co-culture: DMAC was degraded into acetate by HJM-8, then the accumulated acetate was mineralized by YBH-X. Additionally, the co-culture system was further optimized by Box-Behnken design.
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http://dx.doi.org/10.1016/j.chemosphere.2022.134935DOI Listing
September 2022
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